King Pharmaceuticals and FDA reminded healthcare professionals of postmarketing reports of inappropriate use of Bicillin C-R to treat patients infected with syphilis. Bicillin L-A is the only currently approved penicillin G benzathine product indicated for the treatment of syphilis and Bicillin C-R should not be administered in place of Bicillin L-A. Administration of Bicillin C-R instead of Bicillin L-A in the treatment of syphilis may result in inadequate treatment.

In addition, a BLACK BOX WARNING has been added to the prescribing information of both products to emphasize that these products should only be administered by deep intramuscular injection. They are not intended for intravenous administration and inadvertent intravenous administration of penicillin G benzathine has been associated with cardiorespiratory arrest and death.